Dissolved Corneal Extracellular Matrix for Cell Regeneration
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Solution Overview
Problem
Current treatments for corneal disorders, such as dystrophy and recurrent corneal erosion syndrome, are limited due to the lack of pharmaceutical compositions that mimic native corneal tissue components, often resulting in immunogenic responses and limited cell regeneration capabilities, especially for human endothelial cells which do not regenerate.
Innovation Solution
A tissue-derived, dissolved extracellular matrix composition is prepared by dissolving extracted corneas in an aqueous inorganic base solution, then dialyzed to achieve physiological pH, which can be seeded with desired cell types to stimulate cell proliferation and regeneration, and can be cross-linked to form a scaffold for sustained growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If foreign tissue transplants are used to treat corneal disorders, then cell regeneration can be achieved, but immunogenic responses occur
Solution Approach 1:
The patent creates a synthetic extracellular matrix composition that copies the natural corneal tissue environment without using actual foreign tissue. The composition includes collagen, proteoglycans, and other matrix components that mimic native corneal ECM, providing a scaffold for cell regeneration while avoiding immunogenicity associated with allogeneic or xenogeneic tissue transplants
Solution Approach 2:
The patent modifies the physical and chemical parameters of the extracellular matrix composition to optimize cell regeneration. The composition is cross-linked to achieve appropriate mechanical strength and stability, while controlling porosity and degradation rate to support cell proliferation and differentiation without triggering immune responses
2Ease of operation
If traditional pharmaceutical compositions are used, then treatment can be administered, but they fail to mimic native corneal tissue components
Solution Approach 1:
The patent employs a composite extracellular matrix composition containing multiple biomaterials including collagen types I, III, and V, proteoglycans, glycoproteins, and other ECM components. This composite structure replicates the complexity of native corneal tissue, providing both ease of administration as a formulation and high effectiveness in promoting tissue regeneration through multiple synergistic mechanisms
3Manufacturing precision
If corneal tissue is dissolved in strong base solution, then complete dissolution is achieved, but pH must be carefully adjusted to physiological levels
Solution Approach 1:
The patent performs pH adjustment as a preliminary step before final formulation and application. The extracellular matrix composition is first dissolved in a strong base solution to ensure complete dissolution of corneal tissue, then pH is adjusted to physiological levels (7.2-7.4) using buffering agents or acidification before cells are introduced, preventing cell damage while maintaining dissolution efficiency
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The extracellular matrix composition effectively stimulates cell proliferation and regeneration, reducing immunogenic responses and promoting robust attachment and growth of corneal epithelial cells, potentially offering a more effective treatment for corneal disorders without the risks associated with foreign tissue transplants.
Implementation Method 1
The resulting solution is then dialyzed to achieve a physiological pH
Implementation Method 2
the extracellular matrix can be cross-linked chemically to form a scaffold/implant (e.g., glutaraldehyde cross-linked extracellular matrix composition)
Data Source
AI summary
The present disclosure relates to a composition and methods for preparing a tissue-derived, dissolved extracellular matrix. In implementations, the extracellular matrix composition includes components native to the cornea including liquefied corneal tissue. The extracellular matrix composition can be prepared by dissolving extracted corneas in an aqueous solution of inorganic base. The resulting solution is then dialyzed to achieve a physiological pH. In some implementations, the extracellular matrix composition can be seeded and/or chemically cross-linked to form a gel matrix. The extracellular matrix and/or the gel matrix can be seeded with a desired cell type (e.g., endothelial cells, epithelial cells, stromal keratocytes, etc.) to stimulate cell proliferation and regeneration.